CNS lymphoma, the Irish experience: A retrospective review of neuropathologically confirmed cases over 10 years.

BACKGROUND: Central nervous system (CNS) lymphoma is rare, representing 2% of all brain tumors. The commonest subtype is diffuse large B-cell lymphoma (DLBCL), with primary T-cell lymphomas (PCNSTL) accounting for ~ 2%. OBJECTIVE: To determine the frequency and describe the key features of CNS lymphoma over a 10-year period in an Irish population. MATERIALS AND METHODS: This retrospective review was carried out using the neuropathology database in Beaumont hospital, the largest of two national neurosurgical centers, to identify all cases of CNS lymphoma from 2007 to 2017. Clinical, radiological, morphological, immunophenotype, and molecular information was recorded where available. RESULTS: We identified 149 cases of CNS lymphoma from 2007 to 2017, which equated to a cumulative incidence rate of 0.4/100,000 persons. Median age at diagnosis was 66 years, and 46% were male. 86% were classified as DLBCL (n = 128), 10% immunodeficiency-associated CNS lymphoma (n = 15), 3% PCNSTL (n = 4), and 1% (n = 2) cases of intravascular large B-cell lymphoma. Location in declining frequency was as follows: supratentorial (n = 125), infratentorial (n = 22), spinal (n = 1), and orbital (n = 1). CONCLUSION: This is the first study in an Irish population to determine a cumulative incidence rate of CNS lymphoma, which is in line with larger international population-based registries. No significant trends in incidence rate have been observed from 2007 to 2017. DLBCL is the commonest subtype encountered. Rare variants including PCNSTL can pose a significant diagnostic challenge, and in this setting, molecular studies can be useful to confirm diagnoses.

Pheochromocytoma due to a novel SDHD variant presenting as unilateral visual loss.

SUMMARY: A 53-year-old female presented to a tertiary ophthalmology referral centre complaining of unilateral painless loss of vision. Subsequent assessment revealed malignant hypertension causing right-sided cystoid macular oedema. During the course of secondary hypertension workup, she was diagnosed with a 7.8 cm phaeochromocytoma which was resected. Testing for a panel of all predisposing phaeochromocytoma-causing variants using next-generation sequencing resulted in the diagnosis of a novel SDHD variant. LEARNING POINTS: Screening for secondary causes of hypertension is indicated when there is evidence of hypertension-mediated end-organ damage (1). Testing for a predisposing variant should be considered in all patients with phaeochromocytoma or paraganglioma due to the high heritability rate and prevalence of somatic variants (2, 3, 4). Novel variants are commonly uncovered in the Succinate Dehydrogenase (SDH) subunit; proving pathogenicity is a complex, time-consuming process and one challenge of next-generation sequencing (3). SDHB immunohistochemistry as a tool for demonstrating pathogenicity is associated with reduced sensitivity when assessing SDHD variants (5, 6).

Molecular Subtyping of Diffuse Large B-Cell Lymphoma Using a Novel Quantitative RT-PCR Assay.

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease. Cell-of-origin classification in DLBCL has identified activated B cell (ABC) and germinal center B cell (GCB) as two major subtypes. Patients with the ABC subtype show reduced overall survival with standard therapies. Development of a quantitative RT-PCR-based lymphoma cell-of-origin (LCOO) assay to determine ABC, GCB, and unclassifiable subtypes in formalin-fixed, paraffin-embedded tissue (FFPET) DLBCL samples is reported. The LCOO classifier was trained on two DLBCL cohorts with validation performed by using an analytical grade assay in an independent cohort of 60 FFPET DLBCL samples. In the validation cohort, LCOO classification was 88.1%, 84.7%, and 84.7% concordant with microarray, immunohistochemistry (Hans classification), and Lymphoma Subtyping Test, respectively. Importantly, LCOO and Lymphoma Subtyping Test assays commonly assigned subtypes in 17 (94.4%) of 18 ABC samples and 34 (89.5%) of 38 GCB DLBCL samples from this cohort. Progression-free survival and overall survival of ABC and GCB subtypes, as classified by all platforms, were not significantly different in the validation cohort. LCOO classification using publicly available microarray gene expression from two independent data sets (414 fresh frozen and 474 FFPET DLBCL biopsies) revealed a significantly worse outcome for the ABC subtype compared with that of the GCB subtype. Thus, a sensitive, reproducible, LCOO assay developed on an easy to standardize quantitative RT-PCR platform may be an important clinical tool for DLBCL cell-of-origin classification.